Genomics Targets Aggressive Breast Cancer

Robert DavidsonEditor-in-Chief

US Pharm. 2018;43(9):2.

The reach of pharmacogenomics in identifying and treating disease continues to grow. Recently, news broke on how scientists can refine genetic testing for susceptibility to triple-negative breast cancer—a variant associated with particularly poor survival. The study, from the Journal of the National Cancer Institute, pinpoints specific genes associated with increased risk for the aggressive cancer, forming the basis for better risk management.

Triple-negative breast cancer accounts for 15% of cases in Caucasian patients and 35% in African Americans. Triple-negative breast cancer is also associated with high recurrence risk and poor 5-year survival rates. Until recently, identifying women at heightened risk for triple-negative breast cancer was challenging because only inherited mutations in the human tumor suppressor gene BRCA1 were linked to this breast cancer subtype.

In the study, genetic testing was applied to 10,901 patients with triple-negative breast cancer from two studies. Among the genes tested, alterations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D genes were linked to high risk for triple-negative breast cancer and greater than 20% lifetime risk of overall breast cancer in Caucasians. Researchers saw a similar trend among African Americans. In addition, BRIP1 and RAD51C mutations were associated with more moderate risks of triple-negative disease.

Earlier studies uncovered genetic variations in BARD1, BRIP1, PALB2, and RAD51C more frequently in patients with triple-negative breast cancer than in those with other types of breast cancer. The current study, however, expands on this relationship and better highlights a strong association between RAD51D and risk of triple-negative disease. The findings could enable specific genetic testing.

The study results might also lead to revisions to the National Comprehensive Cancer Network guidelines, which recommend only BRCA1/2 testing when a patient has a family history of breast cancer or is diagnosed at age 60 years or younger. A clearer grasp of gene-specific risks for triple-negative breast cancer might help formulate guidelines for testing other susceptibility genes and enable better risk assessment.

“The results from our study showing that multiple genes cause increased risk of triple-negative breast cancer should help in the clinical management of women found to have inherited mutations in these genes,” said study author Fergus J. Couch, PhD, professor and chair of the Division of Experimental Pathology and Laboratory Medicine at the Mayo Clinic.